41222-60-0

Upstream product

• 58452-00-9 3-benzyloxy-4-methoxybenzoic acid 
• 6702-50-7 3-hydroxy-4-methoxybenzoate 
• 645-08-9 Isovanillic acid 
• 100-39-0 benzyl bromide 
• 621-59-0 isovanillin 
• 6346-05-0 3-benzyloxy-4-methoxybenzaldehyde 

Downstream Products

• 146255-82-5 1-(3'-benzyloxy-4'-methoxybenzoyl)-4,6-dimethoxyindole 
• 113332-61-9 N-(4-hydroxy-3-methoxyphenethyl)-4-methoxy-3-benzyloxybenzamide 
• 89456-25-7 3-Benzyloxy-4-methoxy-benzoic acid 2-acetyl-6-benzyloxy-3,5-dimethoxy-phenyl ester 
• 77513-52-1 ethyl 2-(3-benzyloxy-4-methoxybenzoyl)acetoacetate 
• 71146-44-6 Acetic acid 1-(3-benzyloxy-4-methoxy-phenyl)-2-[2-(3-benzyloxy-4-methoxy-phenyl)-2-oxo-acetylamino]-ethyl ester 
• 228869-36-1 3-benzyloxy-N,N-diethyl-4-methoxy-benzamide 
• 916606-20-7 N-(2-fluorophenyl)-3-benzyloxy-4-methoxybenzamide 
• 228869-37-2 3-Benzyloxy-N,N-diethyl-2-formyl-4-methoxy-benzamide 
• 256443-87-5 1-Chloro-6-methoxy-5-(5-phenyl-pent-1-ynyl)-phthalazine 
• 256443-86-4 6-methoxy-5-(5-phenyl-pent-1-ynyl)-2H-phthalazin-1-one 
• 228869-42-9 6-methoxy-5-(5-phenyl-pentyloxy)-2H-phthalazin-1-one 
• 256443-15-9 1-(3,5-dichloro-pyridin-4-ylmethyl)-6-methoxy-5-(5-phenyl-pent-1-ynyl)-phthalazine 
• 89456-32-6 8-Benzyloxy-2-(3-benzyloxy-4-methoxy-phenyl)-5,7-dimethoxy-chromen-4-one 
• 89456-18-8 1-(3-Benzyloxy-2-hydroxy-4,6-dimethoxy-phenyl)-3-(3-benzyloxy-4-methoxy-phenyl)-propane-1,3-dione 

Relevant academic research and scientific papers

METHOD FOR PRODUCING OXAZOLE COMPOUND

An object of the present invention is to provide a novel method for producing an oxazole compound. The invention relates to a method for producing a compound represented by formula (1): wherein R1 is lower alkyl group or halogen substituted lower alkyl group, R2 is lower alkyl group, R5 is lower alkyl group, R11 is lower alkyl group, halogen substituted lower alkyl group or a group represented by formula: -CY2COOR12, wherein Y is a halogen atom, R12 is an alkali metal atom or lower alkyl group, Ar1 is phenyl group substituted with lower alkyl group, etc., or pyridyl group substituted with lower alkyl group, etc., X2, X3 and X9 are the same or different and are halogen atoms, X4 is a leaving group, and M is an alkali metal atom.

Catechol pyrazolinones as trypanocidals: Fragment-based design, synthesis, and pharmacological evaluation of nanomolar inhibitors of trypanosomal phosphodiesterase B1

Trypanosomal phosphodiesterases B1 and B2 (TbrPDEB1 and TbrPDEB2) play an important role in the life cycle of Trypanosoma brucei, the causative parasite of human African trypanosomiasis (HAT), also known as African sleeping sickness. We used homology modeling and docking studies to guide fragment growing into the parasite-specific P-pocket in the enzyme binding site. The resulting catechol pyrazolinones act as potent TbrPDEB1 inhibitors with IC50 values down to 49 nM. The compounds also block parasite proliferation (e.g., VUF13525 (20b): T. brucei rhodesiense IC50 = 60 nM, T. brucei brucei IC50 = 520 nM, T. cruzi = 7.6 μM), inducing a typical multiple nuclei and kinetoplast phenotype without being generally cytotoxic. The mode of action of 20b was investigated with recombinantly engineered trypanosomes expressing a cAMP-sensitive FRET sensor, confirming a dose-response related increase of intracellular cAMP levels in trypanosomes. Our findings further validate the TbrPDEB family as antitrypanosomal target.

Synthesis and biological evaluation of novel 4-indolyl-5-phenyl(indolyl)-1, 2-dihydropyrazol-3-ones as glycogen synthase kinase-3β (GSK-3β) inhibitors

Nineteen novel 4-indolyl-5-phenyl(indolyl)-1,2-dihydropyrazol-3-ones were synthesized and evaluated for their GSK-3β inhibitory activity. Half of the tested compounds showed moderate GSK-3β inhibitory activity. Preliminary structure-activity relationships were discussed, which showed that the presence of 3,4,5-trimethoxy group on the benezene ring enhanced potency while the existence of an electron-withdrawing group at the 4-position of the benezene ring deceased activity. Compounds 11c and 14, the most potent compounds with IC50 values of 9.28 and 8.98 μM, respectively, would be promising candidates for further development of novel GSK-3β inhibitors.

N-benzoylated phenoxazines and phenothiazines: Synthesis, antiproliferative activity, and inhibition of tubulin polymerization

A total of 53 N-benzoylated phenoxazines and phenothiazines, including their S-oxidized analogues, were synthesized and evaluated for antiproliferative activity, interaction with tubulin, and cell cycle effects. Potent inhibitors of multiple cancer cell l

Pharmacological validation of trypanosoma brucei phosphodiesterases B1 and B2 as druggable targets for African sleeping sickness

Neglected tropical disease drug discovery requires application of pragmatic and efficient methods for development of new therapeutic agents. In this report, we describe our target repurposing efforts for the essential phosphodiesterase (PDE) enzymes TbrPDEB1 and TbrPDEB2 of Trypanosoma brucei, the causative agent for human African trypanosomiasis (HAT). We describe protein expression and purification, assay development, and benchmark screening of a collection of 20 established human PDE inhibitors. We disclose that the human PDE4 inhibitor piclamilast, and some of its analogues, show modest inhibition of TbrPDEB1 and B2 and quickly kill the bloodstream form of the subspecies T. brucei brucei. We also report the development of a homology model of TbrPDEB1 that is useful for understanding the compound-enzyme interactions and for comparing the parasitic and human enzymes. Our profiling and early medicinal chemistry results strongly suggest that human PDE4 chemotypes represent a better starting point for optimization of TbrPDEB inhibitors than those that target any other human PDEs.

AMIDE DERIVATIVE

The present invention relates to a compound of the formula (I) being useful as a renin inhibitor, or a pharmaceutically acceptable salt thereof. wherein R1a is a hydrogen atom, an optionally substituted C1-6 alkyl, etc.; R1b is an optionally substituted C1-6 alkoxy, etc.; R1c is a hydrogen atom, an optionally substituted C1-6 alkoxy, etc.; R2 is a hydrogen atom, an optionally substituted C1-6 alkyl, etc.; R3a, R3b, R3c and R3d are independently the same or different, and each is a group of the formula: -A-B (in which A is a single bond, -(CH2)sO-, - (CH2)sN(R4)CO-, etc., B is a hydrogen atom, an optionally substituted C1-6 alkyl, etc.), etc.; R4 is a hydrogen atom, an optionally substituted C1-6 alkyl, etc.; s is 0, etc.; and n is 1, etc.

Application of an amidyl radical cascade to the total synthesis of (±)-fortucine leading to the structural revision of kirkine

A radical cascade initiated by a nitrogen-centred (amidyl) radical was developed, allowing the rapid construction of galanthan frameworks. It was applied to a concise, stereo/regio-selective and tin-free total synthesis of the natural product (±)-fortucin

The total synthesis of (±)-fortucine and a revision of the structure of kirkine

(Chemical Equation Presented) A molecular zipper: The total synthesis of the natural product fortucine relies on a radical cascade process initiated by the generation of a nitrogen-centered (amidyl) radical (see picture). The procedure is concise, and tin

Synthesis of carbon-11 labeled fluorinated 2-arylbenzothiazoles as novel potential PET cancer imaging agents

Fluorinated 2-arylbenzothiazoles are new potential antitumor drugs, which show potent and selective inhibitory activity against breast, lung, and colon cancer cell lines. Carbon-11 labeled fluorinated 2-arylbenzothiazoles may serve as novel probes for positron emission tomography (PET) to image tyrosine kinase in cancers. The preparation of 4-fluorinated 2-arylbenzothiazoles 4-fluoro-2-(3-benzloxy-4-methoxyphenyl)benzothiazole (6a) and 4-fluoro-2-(3,4-dimethoxyphenyl)benzothiazole (6b) was achieved by a modification of Jacobson thioanilide radical cyclization chemistry. Hydrogenolytic cleavage of the benzyl ether group of compound 6a using H2/Pd-C provided the precursor 4-fluoro-2-(3-hydroxy-4-methoxyphenyl)benzothiazole (7) for radiolabeling. Synthesis of radiolabeling precursors and the reference standards 5- and 6-fluorinated arylbenzothiazoles (11c-n) was achieved via the reaction of o-aminothiophenol disulfides with substituted benzaldehydes under reducing conditions. The target radiotracers carbon-11 labeled 4-, 5-, and 6-fluorinated arylbenzothiazoles (3-[11C]6b, 4-[11C]11c, 3-[11C]11c, 5-[11C]11f, 4-[11C]11f, 4-[11C]11i, 3-[11C]11i, 5-[11C]11l, and 4-[11C]11l) were prepared by O-[11C]methylation of the phenolic hydroxyl precursors (7, 11d, 11e, 11g, 11h, 11j, 11k, 11m, and 11n) with [11C]methyl triflate and isolated by solid-phase extraction (SPE) purification in 30-55% radiochemical yields.

Phthalazine derivatives as phosphodiesterase 4 inhibitors

Compounds of formula (I) wherein B is alkylene, amino, CONH or a bond; Cy is optionally substituted phenyl or heteroaryl; R is H, phenyl or (C1-4)alkyl optionally substituted; R1is (C1-6)alkyl or polyfluoro(C1-6)-alkyl; R2is (C4-7)cycloalkyl optionally containing an oxygen atom and optionally substituted; and the N→O derivatives and pharmaceutically acceptable salt thereof are PDE 4 and TNFα inhibitors.